Changes in Survival in De Novo Metastatic Cancer in an Era of New Medicines

Marianne Luyendijk, MSc; Otto Visser, PhD; Hedwig M. Blommestein, PhD; Ignace H. J. T. de Hingh, PhD; Frank J. P. Hoebers, PhD; Agnes Jager, PhD; Gabe S. Sonke, PhD; Elisabeth G. E. de Vries, PhD; Carin A. Uyl-de Groot, PhD; Sabine Siesling, PhD

Disclosures

J Natl Cancer Inst. 2023;115(6):628-635.

Abstract and Introduction

Abstract

Background: Over the past decades, the therapeutic landscape has markedly changed for patients with metastatic solid cancer, yet few studies have evaluated its effect on population-based survival. The objective of this study was to evaluate the change in survival of patients with de novo metastatic solid cancers during the last 30 years.

Methods: For this retrospective study, data from almost 2 million patients diagnosed with a solid cancer between January 1, 1989, and December 31, 2018, were obtained from the Netherlands Cancer Registry, with follow-up until January 31, 2021. We classified patients as with or without de novo metastatic disease (M1 or M0, respectively) at diagnosis and determined the proportion with M1 disease over time. Changes in age-standardized net survival were calculated as the difference in the 1- and 5-year survival rates of patients diagnosed in 1989–1993 and 2014–2018.

Results:Different cancers showed divergent trends in the proportion of M1 disease and increases in net survival for M1 disease (approximately 0–50 percentage points at both 1 and 5 years). Patients with gastrointestinal stromal tumors saw the largest increases in 5-year survival, but we also observed substantial 5-year survival increases for patients with neuroendocrine tumors, melanoma, prostate cancer, and breast cancer.

Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Per cancer type and time period, the number of newly diagnosed patients with de novo metastatic disease and the mean age
Cancer^a	1989–1993, No.	Mean age (95% CI), y	Male, No. (%)	2014–2018, No.	Mean age (95% CI), y	Male, No. (%)	Increase or decrease
Prostate	5477	74 (73 to 74)	5477 (100)	8491	73 (73 to 73)	8491 (100)	↓
Testicular	210	32 (30 to 33)	210 (100)	293	35 (34 to 36)	293 (100)	↑
Thyroid	182	67 (65 to 69)	64 (35)	259	67 (66 to 69)	116 (45)	≠
Breast	2808	64 (63 to 64)	12 (0)	3826	63 (62 to 63)	42 (1)	↓
NET	304	64 (63 to 65)	158 (52)	840	64 (63 to 65)	466 (55)	≠
Vulva/vagina	27	70 (65 to 76)	0 (0)	85	71 (69 to 74)	0 (0)	↑
Melanoma	440	57 (55 to 58)	249 (57)	1041	63 (62 to 64)	639 (61)	↑
Ovarian	1060	66 (65 to 67)	0 (0)	1517	68 (68 to 69)	0 (0)	↑
Corpus uteri	248	69 (68 to 70)	0 (0)	672	70 (69 to 71)	0 (0)
GIST	50	59 (56 to 63)	21 (42)	160	66 (64 to 68)	101 (63)	↑
Rectum	1956	67 (67 to 68)	1159 (59)	3644	66 (66 to 66)	2254 (62)	↓
Cervix uteri	144	59 (57 to 62)	0 (0)	373	58 (57 to 60)	0 (0)	↓
Sarcoma	390	57 (55 to 59)	214 (55)	545	60 (59 to 62)	329 (60)	↑
Colon	4753	68 (68 to 69)	2259 (48)	9332	68 (68 to 68)	4961 (53)	≠
Kidney	1489	65 (64 to 65)	918 (62)	2205	67 (67 to 68)	1467 (67)	↑
HNSCC	97	62 (60 to 64)	77 (79)	238	66 (64 to 67)	178 (75)	↑
Bladder	549	69 (68 to 70)	384 (70)	1768	70 (70 to 71)	1164 (66)	↑
Other solid cancers	811	65 (64 to 66)	364 (45)	1187	65 (64 to 65)	586 (49)	≠
Cancers with an unknown primary site	11 659	69 (69 to 69)	6406 (55)	5280	73 (72 to 73)	2661 (50)	↑
SCLC	3575	66 (65 to 66)	2871 (80)	4873	67 (67 to 68)	2564 (53)	↑
Esophagus/cardia	1646	65 (64 to 65)	1229 (75)	4387	67 (67 to 67)	3464 (79)	↑
Stomach	2720	69 (68 to 69)	1697 (62)	2148	69 (68 to 69)	1329 (62)	≠
NSCLC	7510	65 (65 to 65)	6055 (81)	19 868	67 (67 to 67)	11 262 (57)	↑
Lung other	1045	70 (70 to 71)	874 (84)	2890	76 (75 to 76)	1706 (59)	↑
Bile ducts	289	69 (67 to 70)	133 (46)	1347	67 (66 to 67)	665 (49)	↓
Hepatocellular	114	62 (59 to 65)	69 (61)	508	68 (67 to 69)	395 (78)	↑
Gallbladder	339	71 (70 to 72)	73 (22)	383	70 (69 to 71)	111 (29)	↓
Pancreas	2371	67 (66 to 67)	1288 (54)	6223	69 (69 to 69)	3275 (53)	↑
Total	52 263	67 (67 to 67)	20 002 (62)	84 383	68 (68 to 68)	48 519 (57)	↑

^aSee Supplementary Table 2 (available online) for a detailed description of the cancer types; ↑ = increase; ↓ = decrease; ≠ = remained the same. CI = confidence interval; GIST = gastrointestinal stromal tumors; HNSCC = head and neck squamous cell carcinoma; NET = neuroendocrine tumor; NSCLC = non-small cell lung cancer; SCLC = small cell lung cancer.

Authors and Disclosures

Marianne Luyendijk, MSc^1,2, Otto Visser, PhD³, Hedwig M. Blommestein, PhD², Ignace H. J. T. de Hingh, PhD⁴, Frank J. P. Hoebers, PhD⁵, Agnes Jager, PhD⁶, Gabe S. Sonke, PhD⁷, Elisabeth G. E. de Vries, PhD⁸, Carin A. Uyl-de Groot, PhD² and Sabine Siesling, PhD^1,9,*

¹Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
²Erasmus School of Health Policy & Management, Erasmus University, Rotterdam, the Netherlands
³Department of Registration, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
⁴Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
⁵Department of Radiation Oncology (MAASTRO), Research Institute GROW, Maastricht University, Maastricht, the Netherlands
⁶Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
⁷Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
⁸Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
⁹Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, the Netherlands

*Correspondence to
Sabine Siesling, PhD, Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), PO Box 19079, 3501 DB, Utrecht, the Netherlands (e-mail: s.siesling@iknl.nl; s.siesling@utwente.nl).

Author contributions
Gabe S Sonke, PhD (Writing — review & editing), Agnes Jager, PhD (Conceptualization; Supervision; Writing — review & editing), Elisabeth G E de Vries, PhD (Writing — original draft; Writing — review & editing), Sabine Siesling, PhD (Conceptualization; Investigation; Project administration; Supervision; Writing — original draft; Writing — review & editing), Carin A Uyl de Groot, PhD (Writing — review & editing), Otto Visser, PhD (Conceptualization; Data curation; Formal analysis; Software; Supervision; Writing — original draft; Writing — review & editing), Marianne Luyendijk, MSc (Conceptualization; Formal analysis; Investigation; Methodology; Project administration; Software; Visualization; Writing — original draft; Writing — review & editing), Hedwig M Blommestein, PhD (Conceptualization; Investigation; Supervision; Visualization; Writing — original draft; Writing — review & editing), Frank J P Hoebers, PhD (Writing — review & editing), Ignace H J T de Hingh, PhD (Writing — review & editing).

Conflicts of interest
IHJTH reports research grants or contracts paid to the institute from Roche and RanD Biotechnologies. GSS reports grants or contracts paid to the institute from Agendia, AstraZeneca, Merck, Novartis, Roche, and Seagen; consulting fees from Biovica and Seagen also paid to the institute. EGEV reports grants or contracts paid to the institute for the financial support of clinical trials or contracted research from Amgen, Genentech, Roche, CytomX, G1 Therapeutics, Bayer, Synthon, Servier, Regeneron, and Crescendo; consulting fees paid to the institute (institutional financial support for advisory boards/consultancy) from NSABP, Daiichi Sankyo, and Crescendo Biologics; different roles without financial interests (including no-renumerated activities and public positions): member of the ESMO-MCBS, Chair ESMO Cancer Medicines Working Group, Co-chair RECIST committee, member expert panel for selection of Essential Medicine List WHO. CAU reports grants from Boehringer Ingelheim, Astellas, Celgene, Sanofi, Janssen-Cilag, Bayer, Amgen, Genzyme, Merck, Gilead, Novartis, and Astra Zeneca Roche (outside the submitted work). SS reports a role on the Supervisory Board of PALGA (national Pathology laboratory Archive) and received a personal fee for attending the meetings. Authors ML, OV, HMB, FHPH, and AJ had no conflicts of interest to declare.